Coxiella burnetii is a Gram-negative bacterium and causative agent of Q fever in humans. The bacterium is highly adapted to infect alveolar macrophages and subvert their functions, including the avoidance of TLR recognition, the inhibition of apoptosis and the modulation of diverse vesicle traffic pathways. The virulence of C. burnetii depends on the translocation of bacterial proteins (called effectors) into the host cytoplasm through the Dot/Icm type 4 secretion system (T4SS). Collectively these effectors facilitate the formation of a spacious vacuole that supports bacterial replication. Similar to C. burnetii, Legionella pneumophila also relies on a Dot/Icm T4SS and previous studies have demonstrated that Legionella can translocate C. burnetii effectors through this T4SS. L. pneumophila activates intracellular pathways in macrophages that are not activated during C. burnetii infection. Therefore, we have used L. pneumophila to express C. burnetii effectors and monitor their impact on pathways normally activated during L. pneumophila. A library of L. pneumophila ΔflaA expressing 80 different C. burnetii effectors was constructed and screened for impact on host cell death, cytokine production and virulence in Galleria mellonella. Three C. burnetii effectors that may be involved in the manipulation of macrophage cell death were identified. The overexpression of “Effector 3” by L. pneumophila led to decreased pyroptosis and increased cytokine production in BMDMs. During in vitro infections, overexpression of Effector 3 by L. pneumophila or by C. burnetii in BMDMs or HeLa cells, respectively, showed increased replication of both bacteria. Finally, coinfection assays have demonstrated that the overexpression of Effector 3 delays and decreases host cell death. When ectopically expressed in epithelial cells, Effector 3 specifically localizes to mitochondria and preliminary proteomic analysis indicates that Effector 3 influences the abundance of specific mitochondrial proteins. Thus, we aim to further understand the possible pathway modulated by Effector 3. This study will provide insight into the evasive mechanisms used by intracellular pathogens to control the human host cell.